Novel needle driver for magnetic resonance elastography

ABSTRACT

The present invention is directed toward an acoustic, piezoelectric, electric, electro-mechanical or pneumatically driven surface drum driver, in mechanical engagement with a biopsy or acupuncture needle device and a method for its use for diagnosis of small e.g. 100 microns, tumors via the production of magnetic resonance elastographic images (MRE), without artifact production, in a magnetic resonance imaging (MRI) machine. In a second embodiment, the invention is directed toward an acoustically, pneumatically, piezoelectrically, electrically and/or electro-mechanically driven acupuncture needle, useful for simulating manual single-needle acupuncture treatments via a non-manually manipulated acupuncture needle; and further to a device and process for determination, using twin pneumatically driven surface drivers, of organ stiffness, e.g. brain stiffness, which can be quantified so as to be useful in elucidating and quantifying brain cognitive state, e.g. normal, mild cognitive impairment (MCI) or Alzheimer&#39;s dementia (AD).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/871,731, filed on Oct. 12, 2007, which claims benefit of the filingdate of U.S. Provisional Patent Application No. 60/851,644, filed onOct. 12, 2006, the contents of which are herein incorporated byreference.

FIELD OF THE INVENTION

The inventions described herein relate to an apparatus for sensitive andspecific detection of small tumors, e.g. about 100 microns, particularlywithin the breast, liver, kidney and prostate; and further relate tohighly specific and sensitive methods for utilizing the apparatus inperforming guided needle tissue biopsy, particularly biopsies of thebreast, liver, kidney and prostate; and to use the needle driver as anelectric acupuncture device; as well as to the use of twin pneumaticdrivers for non-invasive analysis of brain stiffness as a method fordiagnosing mild cognitive impairment (MCI) and Alzheimer's disease (AD).

BACKGROUND OF THE INVENTION

Breast cancer represents an internationally recognized public healthconcern, which often manifests itself in grave, and sometimes fatal,consequences for its victims. There is strong clinical evidence thatbreast cancer can be detected in its earliest stages, and that whenfound early, markedly improved results in morbidity and mortality arerealized.

Mammography, clinical breast examination and breast self-examination arethe current methods available for screening and early detection ofbreast cancer.

Mammography screening, although considered to be the “gold standard”,nevertheless suffers from well-known limitations includingover-diagnosis. With optimal technique and patient conditions, it has areported sensitivity between 69% and 90% and a specificity between 10%and 40%.

Many factors, including density of breast tissue (i.e., youngerpatients, implants, and post surgical state) can affect these values.Mammography, when used alone, is believed to miss between 10% and 30% ofall breast cancers. Possible reasons may include density of breastparenchyma (as mentioned above), poor technique and positioning, errorby the reading radiologist, and slow growing breast cancers. Althoughcertain strategies, such as computer-aided detection (CAD) and/orrereading by another radiologist, have been implemented in certaincases, to improve overall detection capability, their impact ondetection of breast cancer is variable, at best. Because the specificityof mammography for characterizing breast lesions is relatively limited,typically 50-75% of the identified abnormalities, when removed forbiopsy analysis, are found to be benign.

Ultrasound has been used as an adjunct to mammography, and is ofparticular value in differentiating cystic from solid lesions and infacilitating guided biopsy of suspicious areas. However, ultrasound hasinherent limitations, including the possibility of missing microcalcifications (associated with ductal carcinoma in situ (DCIS)) anddifficulty in ensuring that the entire breast is imaged with thetransducer.

These limitations have prompted investigators to examine the value ofother imaging modalities such as scintigraphy, contrast-enhanced MRI andMagnetic Resonance Elastography (MRE) for tumor detection andcharacterization.

Magnetic resonance (MR)-guided biopsy is a critical element of anybreast MR imaging capability to ensure optimal patient management. Thepreponderance of studies has demonstrated that this technique has highsensitivity (90-100%) for detecting breast cancer. This exceeds thesensitivity of any other imaging technology. While multiple studies haveestablished that the sensitivity of MR-guided biopsy for diagnosingbreast malignancy approaches 100%, the reported diagnostic specificityhas been generally less favorable, ranging between 65% and 80%.Therefore, further improvements in the diagnostic specificity ofMR-guided biopsy for diagnosing breast cancer is essential to maximizeearly detection and treatment. Specifically, identifying other,independent parameters effective for characterizing MRI-accessibletissue will permit enhanced differentiation of malignancy from benignbreast lesions.

Magnetic Resonance Elastography (MRE) is a new technique useful forassessing the viscoelastic properties of tissue. The MRE technique canquantitatively depict the elastic properties of, e.g. breast tissues invivo and reveal the high shear elasticity in known breast tumors. Sinkusand colleagues described the inversion techniques for breast MRE andapplied the methods to study the mechanical properties of breast tissuesin normal volunteers and patients with breast cancer.

The most obvious potential role for MRE in breast imaging is as apossible method for improving the diagnostic specificity ofcontrast-enhanced MRI. In order to determine whether or not MRE-basedmeasurements of shear stiffness can improve the specificity of lesionclassification in CE-MRI of the breast, in vivo testing would need to beconducted.

The instant inventors have previously designed breast gel phantoms and apiezoelectric motor driven needle driver for needle-guided breast MRE;developed an animal model with breast tumors and made use of the MREdriver at GE 1.5T and 3T MRI system.

The present invention provides an improvement over this previous workwhich utilizes an enhanced, drum driven needle-guided breast biopsydevice, which is particularly constructed and arranged for utilizationwithin an MRI machine, to generate shear waves, necessary to performhighly sensitive and specific MRE analyses, without generation ofartifactual interference, due to the non-metallic nature of the device.Tests of this device have been carried out on human subjects at MRIResearch Lab, Mayo Clinic, Rochester, and Jockey Club MRI Centre, TheUniversity of Hong Kong.

The overall objective of such testing is to demonstrate the ability ofthe instantly disclosed drum driven needle biopsy device to reduceunnecessary biopsies and interventions, by virtue of its increasedsensitivity and specificity in diagnosing invasive breast cancer,especially in women with high hereditary risk.

Both mammography and MRI-guided breast tumor biopsies have beenperformed for more than 25 years, but neither technique is able toelucidate small cancers.

The instantly designed devices are at the forefront of technology inbreast cancer diagnostics. Given the very high resolution provided byMRE images, the MRE needle-guided breast biopsy technique can detectsmall cancers (MRE generates high-amplitude, artifact-free motionthroughout a breast to enable visualization of tumors of less than onehundred microns, a very small tumor, which is unable to be found byeither MR-guided biopsy or mammography. The end-result of thistechnology will be the saving of additional lives, along with areduction in the number of un-wanted biopsy procedures.

MRE surface drivers have previously been used for the detection ofbreast, liver, kidney and prostate tumors via generation of sphericalwaves and piezoelectric bending element driven MRE needle drivers havebeen used for the detection of breast, liver, kidney and prostate tumorsby the generation of plane waves.

Currently, MRE surface drivers have certain limitations. Since they userelatively low frequency, the wavelength is relatively longer. The longwavelength makes it difficult to detect smaller lesions. The instantneedle driver utilizes a much higher frequency range; therefore the wavelength induced by the needle driver is much shorter than that induced bythe surface driver. Additionally, since the needle deeply penetrates thetissue, lesions which are deeply located, or are smaller in size, areable to be detected.

By combining a combination of either acoustic, piezoelectric, electric,electro-mechanical or pneumatically driven surface drum drivers alongwith corresponding needle drivers, it is possible to generate bothspherical and plane waves at the same time. The combined drivers canfurther improve the shear waves and increase the sensitivity andspecificity for the detection of tumors, while again reducingunnecessary biopsies. Simultaneously, it is possible to use the needleto perform biopsies immediately after finding the lesion, thuseliminating an additional invasive step.

The instantly disclosed technology can be used on a variety of MRImachines, including, but not limited to those manufactured by GeneralElectric, Siemens and Philips.

Comparison of Techniques

MR-guided MRE needle biopsy biopsy MR + MRE Specificity 65-80% 90% 95%Adverse reaction Yes No Yes to Gd-DTPA Sequence for No Yes — specimenimaging Needle size larger small larger Small cancer undetectabledetectable —

DESCRIPTION OF THE PRIOR ART

Rossman et al, U.S. Pat. No. 5,952,828, discloses a device for applyingan oscillatory stress to an object positioned in a polarizing magneticfield of an NMR imaging system used together to perform MR elastography.The devices employ electrically energized coils which are connected todrive members and drive plates in a manner to provide variousoscillatory forces to an object being imaged. The different oscillatoryforces enable different body organs to be imaged using MR elastographymethods.

Ehman, U.S. Pat. No. 5,977,770, teaches a scan using an NMR imagingsystem that is carried out while applying an oscillating stress to anobject being imaged. An alternating magnetic field gradient synchronizedwith the applied stress is employed in the NMR imaging pulse sequence todetect and measure synchronous spin motion throughout the field of view.The direction of the alternating gradient and/or the applied stress maybe changed to measure and image the elastic properties of the object.

Feldstein et al., U.S. Pat. No. 4,154,228, discloses an arrangement forand method of inserting a glass microelectrode having a tip in themicron range into body tissue. The arrangement includes amicroelectrode. The top of the microelectrode is attached to thediaphragm center of a first speaker. The microelectrode tip is broughtinto contact with the tissue by controlling a micromanipulator.Thereafter, an audio signal is applied to the speaker to cause themicroelectrode to vibrate and thereby pierce the tissue surface withoutbreaking the microelectrode tip. Thereafter, the tip is inserted intothe tissue to the desired depth by operating the micromanipulator withthe microelectrode in a vibratory or non-vibratory state. A mechanismincluding a second speaker is disclosed. Such mechanism is useful tosense tissue motion to control the microelectrode position with respectthereto substantially constant.

Gardineer et al., U.S. Pat. No. 5,967,991 discloses a disposableinterventional medical device assembly for use with a color ultrasonicimaging system or other ultrasonic systems sensitive to motion. Theassembly includes an interventional medical device having an elongatedmember for insertion into an interior region of a body underinvestigation, and piezo driver assembly coupled to the member of theinterventional medical device. The driver assembly produces a vibratoryoscillation which causes the member to exhibit a flexural motion inresponse thereto, the flexural motion having a zero amplitude point anda maximum amplitude point, wherein the driver assembly is coupled to themember at a point located between the zero amplitude point and themaximum amplitude point of the member's flexural motion. In oneembodiment of the '991 patent, the interventional medical device can bea biopsy needle wherein the elongated member is the shaft of the biopsyneedle. Also described is an ultrasonic imaging system which includesthe earlier described disposable interventional medical device assemblyand a scanner for detecting the flexural motion of the member of thedisposable interventional medical device when the member is insertedinto an interior region of a body under investigation. The systemgenerates an image of the interior region of the body underinvestigation in which the flexural motion is locatively represented.

Gardineer et al., U.S. Pat. No. 5,329,927, discloses a VIBER vibratingmechanism which is coupled to a cannula or needle and operates toprovide flexural vibrations to move the needle and to enable detectionof the position of a needle within a body of interest by a colorultrasound imaging system. The VIBER mechanism exhibits multiple modesof oscillation when energized. The VIBER mechanism is excited to exhibitpredetermined oscillations at a given frequency in the X plane, apredetermined oscillation at another frequency in the Y plane and stillanother frequency of oscillation in the Z plane. In this manner, theVIBER mechanism device exhibits motion in all three planes, which motionis detectable by a conventional color ultrasound imaging system. Thefrequency of oscillation is a function of the entire system, namely theVIBER mechanism, the needle or cannula which is attached to the VIBERmechanism and the tissue. The resonant frequency is preferred as itprovides larger vibrational amplitudes. In this manner, a resonantfrequency is controlled by means of a feedback control loop, whereby thefrequency applied to the VIBER mechanism is monitored to determineresonance and is held at the resonant frequency as the VIBER mechanismor needle is moved. The vibration in the representative planes causes atypical conventional color ultrasound imaging system to display thevibration or movement by means of a color variation. By viewing thedisplay, a system operator, such as a physician can visualize thelocation of the needle because of the color indication provided by thedisplay.

Hofmeier et al., U.S. Pat. No. 6,673,086, discloses an apparatus for themicro-dissection of tissue with a fine needle, which is arranged onholder movable in space along three axes and the tip of which can bemoved with the holder relative to the tissue, which is to be severed,wherein the needle is coupled with an oscillating drive mechanism, whichcauses the needle to oscillate in the longitudinal and/or transversedirection at a predetermined amplitude and frequency.

Powers, U.S. Pat. No. 5,095,910, discloses a system for imaging a biopsyneedle with ultrasound is shown in which the needle tip elicits aDoppler response through controlled reciprocation of the needle tip. Ina preferred embodiment the biopsy needle includes a hollow cannula whichcarries a removable stylet. Means for reciprocating the stylet iscoupled to the proximal end of the stylet, and the distal tip of thestylet is reciprocated at the distal end of the cannula. This motion isdetected through Doppler interrogation of the body region at which thebiopsy is to be performed, and the Doppler response of the needle tip inthe image of the body region allows the needle tip to be monitored as itapproaches the tissue to be biopsied.

Smith, U.S. Pat. No. 6,862,468 is directed toward systems and methodsfor generating MRI elastographs within a blood vessel or organ. In aparticular embodiment, (see col. 2, lines 31-35) an acoustic transducerand RF coil are placed upon a needle, which needle may be inserted in anorgan, e.g. liver or brain, and an elastograph of the region isproduced. This technique differs from the instantly disclosed surfacedrum driver, biopsy needle combination, in that the device of Smith isdesigned for total insertion of the acoustic transducer, RF coil andneedle within the patient, e.g. within a vessel or organ, as opposed toinsertion of only a thin needle as is instantly disclose, therebysubstantially reducing artifactual interference; a technique neithertaught nor suggested by Smith et al.

Ehman, U.S. Pat. No. 7,034,534, teaches a driver for use in applying anoscillating stress to a subject undergoing a magnetic resonanceelastography (MRE) examination which includes a passive actuator locatedin the bore of the magnet and in contact with the subject. A remotelylocated acoustic driver for producing acoustic energy in response to anapplied current, wherein this energy is coupled through a flexible tubeto the passive actuator. A movable element in the passive actuatorvibrates in response to this acoustic energy. Ehman fails to teach orsuggest combining a biopsy or acupuncture needle with any type ofdriver, e.g. an electro-mechanical, acoustic or piezoelectric driver.

SUMMARY OF THE INVENTION

Needle biopsy is a medical test to identify the biological nature of alump or mass, or other abnormal condition in the body. As previouslystated, Magnetic Resonance Elastography (MRE) is a technique forassessing the viscoelastic properties of tissue, via a technique thatimages propagating mechanical waves using MRI. This is performed bysynchronizing motion-sensitive MR imaging sequences with the applicationof acoustic waves in the 50 to 1000 Hz range

We have treated alternative tissues such as the liver, brain and breast.Illustrative examples are included herein, which utilize MRE of breastand brain tissue as enabling, albeit non-limiting embodiment, forpracticing the invention.

Breast MRE technique can quantitatively depict the elastic properties ofbreast tissues in vivo and reveal high shear elasticity in known breasttumors.

As an illustrative embodiment, the present invention provides a drumdriven needle-guided breast biopsy device, constructed and arranged forutilization within an MRI machine so as to preclude generation ofunwanted artifacts. Generation thereby of shear waves, enable theperformance of highly sensitive and specific identification of lesionsfound in breast, liver, kidney and prostate tissues via MagneticResonance Elastography (MRE).

In one particular arrangement, the instant invention enables thecombination of both surface and needle drivers for simultaneouslyproducing spherical and plane waves, which results in a highly sensitiveand specific test, and concomitantly leads to a reduction in theperformance of unnecessary biopsies.

In an exemplary, albeit non-limiting embodiment, a surface driver caninitially be used for the gross detection of possible tumor sites, andthen a needle driver may be used to increase the sensitivity andspecificity by providing an enhanced acoustic wave with a high degree ofpenetration. When very high shear wave tissue is found via thistechnique, which tissue is understood to have a higher probability ofbeing a tumor, the needle driver can instantly function as a biopsyneedle to reduce further invasive techniques and interventions, and toincrease the sensitivity and specificity in diagnosing invasive breast,liver, kidney and prostate cancer.

In addition to the use of the needle driver of the present invention asa means for enhancing MRI diagnostic ability via the enablement of MREelastographs of high sensitivity and specificity, the instant inventorhas also determined that an acupuncture needle, when drivably engagedvia one or more of an acoustic, pneumatic, piezoelectric, or electromechanical driver mechanism, induce mechanical waves within the bodytissue, and thereby provide a functionality, using a single needle,which closely resembles that induced manually by an acupuncturist. Asopposed to presently available electrical acupuncture systems, whichrequire at least two needles, so as to provide a positive and negativepole, the present device provides a non-manual acupuncture system whichoperates in a manner most similar to traditional manual acupuncturetechniques.

It is understood that MRE uses a conventional MRI system to assess theelastic properties of tissues. To generate shear waves in tissue, thereare differing types of drivers: a pneumatic driver, a piezoelectricdriver, an electromagnetic driver, and the like, which in combinationwith any suitable wave generation means, can generate the types ofspherical or planar waves necessary for diagnostic processes. When usinga pneumatic driver, usually it is sufficient to place one driver at onelocation on the tissue. However, we have found that the shear wavegenerated by one pneumatic driver has difficulty in illuminating a largearea like the whole brain or liver due to wave attenuation. In order tocompensate for the wave attenuation, the instant inventors have furtherdiscovered that it is beneficial to use twin pneumatic drivers. It hasbeen our experience that twin pneumatic drivers can compensate for theshear wave attenuation in phantom as well as in human brain.

It is therefore an objective of the instant invention to provide an MREbiopsy system which has much higher specificity and sensitivity thanMR-guided biopsy.

It is another objective of the instant invention to provide a systemwhich is a useful adjunct to contrast-enhanced MRI to diagnose andcharacterize breast cancers.

It is yet another objective of the instant invention to provide a systemhaving a sequence for specimen imaging, so it can be used to make aconfirmation for cancer tissue.

It is still another objective of the instant invention to provide asystem which uses relatively small biopsy needles, in order to reducethe invasiveness and pain associated with the test.

It is yet an additional objective of the instant invention to provide asystem to detect small cancers that cannot be found by other breastbiopsy techniques.

It is yet a further objective of the instant invention to provide anon-manual acupuncture system, utilizing, either singly, or in anycombination, acoustic, piezoelectric, pneumatic and electro-mechanicaldrivers for single acupuncture needles, whereby operation thereofprovides vibratory stimulation in a manner most similar to traditionalmanual acupuncture techniques.

It is a still further objective of the instant invention to teach amethod of accurately determining brain stiffness via the use of twinpneumatic drivers for the purpose of diagnosis, monitoring, elucidatingthe presence of early onset mild cognitive impairment and/of Alzheimer'sdisease, and to provide a non-invasive protocol for determining theprogression and/or response of the condition to pharmacologicalintervention.

The overall objective of the invention remains the reduction ofunnecessary biopsies and interventions, and providing increasedsensitivity and specificity of MRE imaging, for diagnosing breast,liver, kidney, brain and prostate cancer; as well as the overallcondition, as a function of organ stiffness, of a particular organ.

Other objects and advantages of this invention will become apparent fromthe following description taken in conjunction with any accompanyingdrawings wherein are set forth, by way of illustration and example,certain embodiments of this invention. Any drawings contained hereinconstitute a part of this specification and include exemplaryembodiments of the present invention and illustrate various objects andfeatures thereof.

BRIEF DESCRIPTION OF THE FIGURES

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

FIG. 1 shows a prior art mechanically driven biopsy device andassociated needle system;

FIG. 2 shows a perspective view of a drum driver device and biopsyneedle, for use in an MRI machine;

FIG. 3 shows alternative cross-sectional views of the drum driver deviceof FIG. 2;

FIG. 4 shows an experimental setup for breast cancer MRE using the drumdriver of FIG. 2;

FIGS. 5-8 show comparative results obtained by MRE analysis using Needleand Surface drivers, for a Phantom target, Rat, Rabbit and Humantissues;

FIG. 9 references a cross-sectional view of a mechanically driven needlebiopsy device and associated needle system;

FIG. 10 shows a liver/kidney/prostate fixture and a breast fixture;

FIG. 11 shows a set of sample biopsy needles including an outer hollowneedle and inner needle;

FIG. 12 shows an electro-mechanically driven acupuncture or biopsyneedle;

FIG. 13A, 13B and 13C show the results of MRE using twin pneumaticdrivers on normal (13C), MCI (13B), and AD (13A) patients;

FIG. 14 show relative brain stiffness for subjects suffering fromvarious mental impairment versus normal subjects;

FIG. 15 shows a porcine gel phantom with a higher percentage porcineinclusion where the biopsy needle is inserted within he inclusion;

FIGS. 16A and 16B show respectively transverse and coronal images of theporcine gel phantom and inclusion of FIG. 15;

FIG. 17A, 17B, 17C and 17D depict transverse stiffness images using thebiopsy needle driver (A); Transversal wave images using the biopsyneedle driver (B); Coronal stiffness images using the biopsy needledriver (C), (the area in the white circle is the inclusion); the profileof stiffness of the phantom with inclusion (green lines) (D).

FIG. 18A, 18B and 18 c show the T2, T1W and T1W STIR images respectivelyof a rabbit leg with a biopsy needle inside the tumor lesion;

FIGS. 19A and 19B respectively depict an anatomy image of a rabbit legwith tumor and an elastogram of a rabbit muscle with tumor;

FIG. 20 is a graph of Stiffness value under different frequency, whereinthe upper line represents stiffness of tumor and the lower linerepresents stiffness of normal muscle.

DETAILED DESCRIPTION OF THE INVENTION

FIGS. 1 and 9 reference a cross-sectional view of a mechanically drivenneedle biopsy device and associated needle system.

FIG. 2, is a perspective view of a drum needle driver embodiment, inaccordance with the present invention, which can be used as a mechanicalstimulus in MRE for producing a plane wave, as opposed to a sphericalwave as is produced by a surface driver. The drum driver is formed fromany polymer which is safe to use within an MRI machine, e.g.polycarbonate, high density polyethylene, polypropylene,ethylene-propylene copolymer, nylon, and the like. The drum needledriver includes a housing 20, which has an inlet end 22 for influx of apulsatile flow of gas, e.g. air, nitrogen or the like, or the energyoutput supplied by an alternative wave generation means, e.g. a speaker(not shown) which impacts upon diaphragm 24, and causes a rhythmicundulation of the diaphragm 24, and a concomitant movement of the biopsyneedle 26, which is in removable mechanical engagement with thediaphragm via a coupling member 28, at a frequency determined by thepulsatile frequency of the gaseous flow. The resulting MRE is able toyield a higher degree of accuracy in measurement of small tumors, e.g.100 microns, by virtue of the enhanced specificity and sensitivityvisible in the elastographic imaging resulting from the needle generatedplane waves. A comparison of the imaging produced by the surface driverversus needle driver is shown in FIG. 5-8 for a phantom, rat, rabbit andhuman, respectively.

FIG. 3 shows alternative cross-sectional views of the needle drum driverdevice of FIG. 2, which more specifically illustrate the diaphragm 24,housing 20, inlet for source of wave generator 22, and needle elementholder 28.

As earlier alluded to, this technique can be employed for needle-guidedbiopsy in patients with breast, liver, kidney, brain and prostatetumors.

In a preferred, albeit non-limiting embodiment, a needle driverconstructed and arranged for use within an MRI machine, and particularlyconstructed and arranged for performing needle-guided MRE biopsy isillustrated in FIGS. 2 and 3. A set of needles is provided (see FIG. 11)which are interchangeable, and may be selected as needed, specific tothe particular tissue biopsy being performed. The needle driver producesplane acoustic waves orthogonal to the needle. In one embodiment, ifdesirable, an additional surface driver (see FIG. 4), may be added toproduce waves normal to the point of contact and parallel to the needle.Both devices are suitable for MRE imaging, without production ofunwanted artifacts, and the needle has an additional utility in that itcan be used for biopsy.

FIG. 4 shows a patient positioned within an MRI device (MRI device notshown) in an experimental setup for breast cancer MRE using a surfacedriver 42, wherein the pulsatile frequency of the drum driver (e.g.acoustic or pneumatic, or the like) is transmitted to the surface of thebody, in this case the breast 40, to enhance the MRE image. Insertion ofa needle drum driver, as illustrated in FIG. 2, is practiced wherein theneedle is positioned parallel to the surface driver, to produce asensitive imaging platform, absent artifacts, as described above.

The prior version of the invention provided a biopsy needle driver asshown in FIGS. 1 and 9. It consists of a piezoelectric bending element 3for the vibration of the contact plate 6 and the needle 5. The surface(cross section at AA′) 8 a of the contact plate will attach to the skinof the subject for the surface vibration. The piezoelectric bendingelement 3 is held by the holder 1 and connects to power supply 2. Afixation 4 is attached to the center of the Piezoelectric bendingelement for holding the biopsy needle 5. A contact plate 6 for givingthe vibration at the surface of skin is fixed to the fixation 4 by nylonscrew 7. FIG. 9 also shows the cross section of the contact plate 9 a atAA′ from the top view.

FIG. 10 shows a liver/kidney/prostate fixture 10 and a breast fixture12. The patient lays supine for liver and prostate biopsy and lays pronefor kidney and breast biopsies. Two knobs at each side of theliver/kidney/prostate fixture are used for adjusting the height of thefixture. The liver/kidney/prostate fixture is fixed to the table of MRIscanner 10 a. Twenty holes 10 b on the cross section from the BB′ viewsare designated for the different locations of the liver/kidney/prostatein individuals. An inclined plane 11 for holding the needle driver canbe put on the each side of the breasts according to the location of thelesion. The inclination angle of the inclined plane can be adjusted tofit in with the angle of biopsy needles.

FIG. 11 shows a set of sample biopsy needles including an outer hollowneedle 14 and inner needle 13. The handle 16 of the inner needle isattached to the proximal end 17 of the outer hollow needle to form thebiopsy needle 15. An inner needle 13 is slid to engage within the lumenof outer hollow needle 14. There are 20 kinds of biopsy needle availablewith different inner diameters (12, 14, 16, 18 and 20 gauge) anddifferent lengths (10, 13 16 and 20 cm).

FIG. 12 shows an electro-mechanically driven acupuncture or biopsyneedle. Using this technique, or the acoustically, pneumatically orpiezoelectrically driven embodiments outlined herein, induced waves by amoving needle can be generated, thereby simulating the up and downmovement of physical acupuncture treatment. One could then evaluate theinduced waves of simulated acupuncture via MRE, to thereby study, invivo, the efficacy of various acupuncture techniques.

Additional Examples

Human Brain Study

Comparison of the Brain Stiffness Among Normal Subject, MCI Patient andAD Patient Using Magnetic Resonance Elastography with Twin Drivers usingthe 3T GE MRI Systems in Beijing Neurosurgical Institute.

Study Purpose

To develop a new technique based on the state-of-the-art in MagneticResonance Elastography (MRE) for early detection and diagnosis of MildCognitive Impairment (MCI) and Alzheimer's Disease and for establishinga standard range of brain viscosity and elasticity in normal subjects,MCI patients and AD patients.

Methods

As illustrated in FIGS. 13C, 13B and 13A respectively, MRE brain imagesof 4 normal subjects, 2 MCI (mild cognitive impairment) and 5 AD(Alzheimer's dementia) patients were obtained using a GE 3 T MRIscanner. A commercial brain coil was used in the 3T GE MRI systems inBeijing Neurosurgical Institute. Mechanical oscillation was produced bya homebuilt transducer. Typical excitation frequency for in vivomeasurements was 40 Hz. The pulse generator was triggered via thestandard trigger output channel of the spectrometer. The differentcomponents of the mechanical wave were measured using the modifiedspin-echo pulse sequence developed by Mayo Clinic. MREview developed inMayo Clinic was used for data acquisition and reconstruction.

More specifically, it is generally only necessary to utilize a singlepneumatic driver. However, when illuminating a large organ, such as thebrain, the shear wave generated by one pneumatic driver is insufficientto illuminate the whole area due to wave attenuation. In order tocompensate for the wave attenuation, we have found it useful to use twinpneumatic drivers. We have determined that the use of twin pneumaticdrivers can compensate for the shear wave attenuation propagated whenilluminating a human brain with a single pneumatic driver.

In practice, a speaker drives air which propagates in an attached tubeconnected to the driver. The membrane of the driver is placed on theskull and vibrates to generate a shear wave propagating in the brain.The drum-like driver and tubes are made of plastic and are safe for usein the MRI device.

We place two pneumatic drivers symmetrically on the both sides of theskull. The two pneumatic drivers are driven synchronously by the samesource. When comparing the wave pattern images at a particularfrequency, e.g. 100 Hz excitations, generated by a single pneumaticdriver and twin pneumatic drivers respectively, we have observed thatthe shear wave generated by single pneumatic driver exhibitsunacceptable attenuation. In both cases, the pneumatic drivers aredriven at the same frequency and same power. The twin pneumatic driversgenerate an interference wave pattern which can compensate theattenuation effectually. A stiffness value is generated from these data(see for example FIG. 14).

Results

Compared with normal subjects (FIG. 13C), the brain stiffness of bothwhite matter and grey matter is lower in MCI patients (FIG. 13B). Alsothe brain stiffness is lower in AD patients (FIG. 13A) than in MCIpatients (FIGS. 13 and 14). The technique is potentially valuable forearly detection and diagnosis of MCI and Alzheimer's disease. Inaddition, the technique provide a pathway for understanding thepathology of the disease, monitoring disease progression and testing theeffects of drug treatment.

Conclusions

The data demonstrates that the MRE technique is highly valuable forearly detection and diagnosis of Alzheimer's disease and forunderstanding its pathology, monitoring disease progression andeffectiveness of drug treatment. Also, it may provide greater hope forMCI patients for the prevention of the development of AD, since, at avery early stage, MCI is reversible or can be slowed pharmacologically,wherein there is currently no effective pharmacological intervention forAD.

Tumor Detection in Rabbit

MRE is a phase contrast imaging technique to quantitatively measure theelasticity of tissues. Typically, an oscillating driver is placed on thesurface to generate the shear waves. In measuring depth penetration ofthe shear wave in MRE, such measurement is limited by attenuation.Referring to FIGS. 15, 16A and 16B, the instant inventors utilized abiopsy needle as the driver to detect the 15% porcine gel inclusion in a10% porcine gel phantom which simulates a tumor in tissues as well as inthe model of rabbit with tumor in vivo. It is shown that the biopsyneedle driver can accurately measure the stiffness and location of thetumor. An additional benefit is that the biopsy procedure may be carriedout at the same time.

Many lives can be saved when human have routine X-ray, CT or MRIexaminations of the breast, liver and kidney that can detect breast,liver and kidney cancer in its earliest, most curable stages. However,most of the abnormalities seen on those techniques are not cancer. Themost common practice to make a diagnosis is to perform a biopsy in whicha sample of tissue is removed from the breast/liver/kidney for analysis.In the past, it required surgical operation that was painful anddisfiguring. Today, interventional radiologists often can make adiagnosis without surgery with a technique called needle biopsy. In thistechnique, an ultrasound needle is used to remove small samples oftissue from the breast. It is less painful, much less disfiguring (thereis no scar, MRI guided core biopsy left a large scar in the biopsyregion) and requires a shorter recovery time than surgical biopsy, butthe specificity is low.

The present inventors have designed a needle driver for needle-guidedbreast, liver and kidney MRE in human subjects. The overall objective isto reduce the unnecessary biopsies and interventions, and increase thesensitivity and specificity in diagnosing invasive breast, liver andkidney cancer. The purpose of this study was to justify whether shearwaves caused by an inserted biopsy needle can accurately detect andlocate the position of tumors.

Materials and Methodology

Driver Design

The electromechanical driver with a biopsy needle is shown in FIG. 12.The biopsy needle (COOK MRE) was 0.73 mm diameter and MRI compatible.One side of the needle is fixed to the driver and the other side of theneedle is inserted into the phantom. The amplified sinusoidal signal wasinput into the excitation coil. Then signal was synchronized to theimage sequence and triggered by the pulse sequence. The alternativecurrent creates a magnetic field which is perpendicular with the mainmagnetic field. This causes oscillation along the vertical direction.The oscillating motion will be transmitted to the phantom by the needleand the propagating shear wave is observed.

Design of Phantom:

10% porcine gel phantom was used in the experiment to simulate thetissue. A cylindrical 15% porcine phantom of 20 mm diameter was includedin the phantom to simulate the tumor as shown in FIG. 15.

In-Vivo Animal Study:

A female New Zealand white rabbit (6 months old, 4.2 kg) was used inthis study. Animal research ethics approval was obtained and theinstitute's guidelines for the care and use of laboratory animals wereobserved. A VX2 hepatocarcinoma lump with the volume of 1 cm×1 cm×1 cmwas implanted into the left thigh muscle 15 days before the experimentto grow for the tumor. The rabbit was anesthetized with the mixture ofKetamine 10% (at dose of 150 mg/kg, ALFASAN, Woerden-Holland) andXYLAZINE 2% (ALFASAN, Woerden-Holland) at 2:1.

Measurement:

The experiment was done in a Philips Intera Achiva 3T system with SENSEFlex-M surface coil. MRE uses a phase-contrast technique to image theshear wave. The MRE sequence also uses motion sensitizing fieldgradients which are synchronized to the propagating waves. The Field OfView (FOV) is 160 mm. Matrix size is 80×80. TE/TR=25 ms/243 ms. Slicethickness is 2 mm. We set the excitation frequency at 150 Hz. Thestiffness of the phantom is calculated using the equation: μ=ρf²λ² whereρ is the density of the phantom, f is the excitation frequency of thedriver and λ is the shear wavelength measured from the wave images.

TABLE 1 Stiffness Value of the inclusion and background Mean ± StandardDeviation (kPa) Inclusions Background Biopsy 19.05 ± 2.53 12.88 ± 1.42needle

FIGS. 17A, 17B, 17C and 17D depict transverse stiffness images using thebiopsy needle driver (A); Transversal wave images using the biopsyneedle driver (B); Coronal stiffness images using the biopsy needledriver (C), (the area in the white circle is the inclusion); the profileof stiffness of the phantom with inclusion (green lines) (D).

FIGS. 18A, 18B and 18 c show the T2, T1W and T1W STIR imagesrespectively of a rabbit leg with a biopsy needle inside the tumorlesion;

FIGS. 19A and 19B respectively depict an anatomy image of a rabbit legwith tumor and an elastogram of a rabbit muscle with tumor;

FIG. 20 is a graph of Stiffness value under different frequency, whereinthe upper line represents stiffness of tumor and the lower linerepresents stiffness of normal muscle

TABLE 2 Stiffness Value of the tumor and muscle Mean ± StandardDeviation (kPa) Tumor Muscle Biopsy 3.62 ± 1.83 1.03 ± 0.22 needle

DISCUSSION AND CONCLUSION

The experimental result shows that the vibrating biopsy needle cangenerate propagating waves to differentiate phantoms with differentdensities and the phenomenon is observed in MRE in this experiment.Traditionally, surface drivers are used to generate shear waves.However, the shear wave produced by the surface driver may attenuatesignificantly before reaching the deeper tissues. By using the biopsyneedle, this difficulty can be overcome and we can measure the stiffnessof tissues in deep location. Another merit of the biopsy needle is thatwe can directly use it to sample the abnormalities for further analysison a desired site by making use of the MRE image. This technology can beused for needle-guided biopsy in patients with breast, liver and kidneylesions.

In addition to the experiment with phantom, we have performed in-vivoanimal study. FIG. 18 A-C show the T2W and shear wave images with thebiopsy needle inserted into the leg of normal rabbit at 100 Hz. Theresult illustrates that the biopsy needle driver can provide a clearpropagating wave pattern in the muscle of rabbits. FIG. 19 A-B shows theT2W image and elastogram with the biopsy needle inserted into the legwith tumor at 85 Hz. Table 2 shows the stiffness value of the tumor andmuscle. The distance between the needle and the edge of the tumor is 5mm. From the elastogram, we can clearly see the tumor region has higherstiffness value than the muscle. The location of the tumor can be easilyidentified. Thus the biopsy needle as MRE driver can be a good tool toprecisely detect and localized tumors.

It is intended that the specification, drawings and examples can beconsidered as exemplary only, with the true scope and spirit of theinvention being indicated by the following claims. It should beunderstood that only the preferred embodiments have been shown anddescribed and that all changes and modifications that come within thespirit of the invention are desired to be protected.

All patents and publications mentioned in this specification areindicative of the levels of those skilled in the art to which theinvention pertains. All patents and publications are herein incorporatedby reference to the same extent as if each individual publication wasspecifically and individually indicated to be incorporated by reference.

It is to be understood that while a certain form of the invention isillustrated, it is not to be limited to the specific form or arrangementherein described and shown. It will be apparent to those skilled in theart that various changes may be made without departing from the scope ofthe invention and the invention is not to be considered limited to whatis shown and described in the specification and any drawings/figuresincluded herein.

One skilled in the art will readily appreciate that the presentinvention is well adapted to carry out the objectives and obtain theends and advantages mentioned, as well as those inherent therein. Theembodiments, methods, procedures and techniques described herein arepresently representative of the preferred embodiments, are intended tobe exemplary and are not intended as limitations on the scope. Changestherein and other uses will occur to those skilled in the art which areencompassed within the spirit of the invention and are defined by thescope of the appended claims. Although the invention has been describedin connection with specific preferred embodiments, it should beunderstood that the invention as claimed should not be unduly limited tosuch specific embodiments. Indeed, various modifications of thedescribed modes for carrying out the invention which are obvious tothose skilled in the art are intended to be within the scope of thefollowing claims.

1. A process for early detection and diagnosis of Mild CognitiveImpairment (MCI) and Alzheimer's Disease (AD) and to establish astandard range of brain viscosity and elasticity in normal subjects, MCIpatients and AD patients comprising: positioning a patient within amagnetic resonance imaging (MRI) device; providing a pair of pneumaticdrum drivers useful within said MRI device, each driven synchronously bya single wave generator; positioning said pair of pneumatic drum driversin contact with the patient's skull, thereby simultaneously generating ashear wave, and a corresponding interference wave effective toneutralize attenuation of said shear wave, each wave propagating in thebrain; elucidating brain stiffness data as a function of shearwavelength; and establishing a standard range of brain viscosity andelasticity in normal subjects, MCI patients and AD patients; whereincorrelating brain viscosity and elasticity in normal, MCI and ADpatients enables early detection and diagnosis of Mild CognitiveImpairment (MCI) and Alzheimer's Disease (AD).
 2. A process for earlydetection and diagnosis of cancerous tumors in a patient in need of suchdiagnosis comprising: positioning a patient within a magnetic resonanceimaging (MRI) device; providing at least one acoustic, piezoelectric,electric, electro-mechanical or pneumatically driven surface drumdriver, useful within said MRI device, in mechanical engagement with abiopsy or acupuncture needle; inserting said biopsy or acupunctureneedle within a tissue suspected of containing a cancerous tumor;providing wave generating Means for synchronous movement of said biopsyor acupuncture needle within said tissue; generating a magneticresonance elastograph; and elucidating the presence of cancerous tumorsin said patient.
 3. The process of claim 2, further including providingan additional acoustic, piezoelectric, electric, electro-mechanical orpneumatically driven surface drum driver in contact with said patient,in an area adjacent said acupuncture or biopsy needle; wherein bothspherical and plane waves are generated, thereby enhancing specificityand sensitivity.
 4. The process of claim 2, further including the act ofconducting a biopsy by use of the biopsy needle.
 5. A device for earlydetection and diagnosis of cancerous tumors in a patient in need of suchdiagnosis comprising: at least one acoustic, piezoelectric, electric,electro-mechanical or pneumatically driven surface drum driver, usefulwithin an MRI device, in mechanical engagement with a biopsy oracupuncture needle; and a wave generating means for synchronous movementof said biopsy or acupuncture needle; wherein actuation of said wavegenerating means causes movement of said acoustic, piezoelectric,electric, electro-mechanical or pneumatically driven surface drumdriver, which in turn, causes reciprocal movement of said biopsy oracupuncture needle, thereby generating a shear wave within thetissue'being examined; whereby relatively small cancerous tumors ofapproximately 100 microns in size may be visualized by generation of amagnetic resonance elastograph.
 6. A single-needle mechanicalacupuncture device comprising: an acoustic, piezoelectric, electric,electro-mechanical or pneumatically driven surface drum driver, inmechanical engagement with an acupuncture needle; and a wave generatingmeans for synchronous movement of said acupuncture needle; whereinactuation of said wave generating means causes movement of saidacoustic, piezoelectric, electric, electro-mechanical or pneumaticallydriven surface drum driver, which in turn, causes reciprocal movement ofsaid acupuncture needle.